Mussel-inspired dopamine-CuII coatings for sustained in situ generation of nitric oxide for prevention of stent thrombosis and restenosis

Abstract

Nitric oxide (NO) is a highly potent, yet short-lived bioactive molecule with a broad spectrum of physiological functions. Continuous and controllable in situ generation of NO from vascular stent surface can effectively prevent restenosis and thrombosis after its implantation. In this study, inspired by the adhesion and protein cross-linking in the mussel byssus, through immersing the stents into an aqueous solution with dopamine (DA) and copper ions (CuII), we developed a one-step metal-catecholamine assembled strategy to prepare a durable in situ NO-generating biomimetic coating (DA-CuII). Due to the high NO catalytic efficacy and robust chelation of CuII into the DA-CuII network, the coated stents exhibited excellent hemocompatibility. The coating also catalytically decomposed endogenous S-nitrosothiols (RSNOs) from fresh blood, and locally generated NO for over 30 days with a flux comparable to its physiological range (0.5–4 × 10−10 mol × cm−2 × min−1). Moreover, the optimized biomimetic coatings displayed specific cell selectivity to significantly enhance endothelial cell (EC) growth while substantially inhibit smooth muscle cell (SMC) growth and migration. This feature impressively promoted regeneration of a new endothelial cell layer after stent implantation, hence improved the anti-thrombogenic and anti-restenosis qualities of vascular stents in vivo. We envision that our long-term in situ NO-generating coatings could serve as biosurfaces for long-term prevention of stent thrombosis and restenosis.